Genetics and Cancer: Key Concepts and Mechanisms

What is the human genome?

The complete set of genetic information in a human cell.

What is a phenotype?

The physical manifestation of an inherited trait or disease.

What is a genotype?

The genetic makeup of a person.

How do genotypes and phenotypes change in cancer?

Both genotype and phenotype keep changing over time.

What is a mutation?

A change in the normal base pair sequence of DNA that can alter protein function.

What are germline mutations?

Mutations present in egg or sperm that are heritable and can cause cancer family syndrome.

What are somatic mutations?

Mutations that occur in nongermline tissues and are nonheritable.

What is the difference between point mutations and frameshift mutations?

Point mutations involve a single base pair change, while frameshift mutations involve insertions or deletions that alter the reading frame.

What is penetrance in genetics?

The proportion of individuals with a specific genotype that express the associated phenotype.

What factors can influence penetrance?

Carcinogens, modifier genes, and hormonal factors can influence penetrance.

What is the role of noncoding regions in genes?

Noncoding regions, such as introns, do not code for proteins but play roles in gene regulation.

What is apoptosis?

A process of programmed cell death that can be triggered by cell damage or loss of growth control.

What is the significance of the Her2 gene in cancer?

Her2 gene amplification is associated with aggressive breast cancer and high risk of relapse.

What is neoplasia?

Abnormal tissue growth characterized by uncontrolled cell proliferation.

What distinguishes benign tumors from malignant tumors?

Benign tumors grow locally and are rarely life-threatening, while malignant tumors spread and are often life-threatening.

What are the major types of new tissue growth?

Neoplasia, dysplasia, hyperplasia, and hypertrophy.

What is the role of transcriptional control in gene expression?

Transcriptional control regulates the initiation of gene transcription, influencing protein production.

How do epigenetic factors affect gene expression?

Epigenetic modifications, such as DNA methylation, can activate or silence genes without altering the DNA sequence.

What is the difference between normal and neoplastic growth?

Normal growth is organized and regulated, while neoplastic growth is disorganized and uncontrolled.

What is a fusion protein?

A protein created from the joining of two different genes, often associated with cancer.

What is the role of ribosomes in protein synthesis?

Ribosomes translate mRNA into proteins by linking amino acids together.

What is the significance of chromosome aberrations in cancer?

Chromosome aberrations can lead to genetic instability and contribute to cancer progression.

What is the impact of repair failure on cancer development?

Repair failure of DNA damage can lead to mutations and chromosomal instability, increasing cancer risk.

What is anchorage independent growth?

A characteristic of cancer cells that allows them to grow without being attached to a surface, leading to insensitivity to population density.

How do cancer cells differ from normal cells in terms of growth?

Cancer cells can grow in soft agar or suspension and lose contact inhibition, while normal cells grow in monolayers and stop dividing when crowded.

What is the significance of immortalized cancer cells?

Immortalized cancer cells, such as HeLa cells, can divide indefinitely and maintain telomere length.

What are common defects found in cancer cells?

Defects in signaling pathways, cell cycle controls, and apoptosis, allowing proliferation without growth factors and disruptions in cell cycle control.

What are the three main types of cancers based on cell origin?

1. Carcinomas (epithelial cells), 2. Sarcomas (supporting tissues), 3. Lymphomas/Leukemias (hematopoietic derived).

What is the naming convention for benign tumors?

Benign tumors are typically named with the suffix '-oma'.

What suffix is used for malignant tumors of epithelial origin?

Malignant tumors of epithelial origin are named with the suffix '-carcinoma'.

What is angiogenesis in the context of tumors?

Angiogenesis is the process by which tumors stimulate the growth of new blood vessels to supply nutrients and oxygen.

What is the significance of the 'seed and soil' hypothesis in cancer metastasis?

It suggests that certain cancer cells (seeds) can only grow in specific environments (soil) that support their growth.

What are carcinogens?

Carcinogens are substances that can cause cancer, such as those found in coal tar and cigarette smoke.

What role do retroviruses play in cancer?

Certain retroviruses, like Human T-cell leukemia virus (HTLV-1), can cause cancer by integrating into the host genome.

What is the Ames test used for?

The Ames test measures the mutagenic activity of a chemical, indicating its potential to cause cancer.

What are caretaker genes?

Caretaker genes are involved in DNA repair and help restrain cell proliferation.

What are gatekeeper genes?

Gatekeeper genes control cell growth and division, preventing uncontrolled proliferation.

What is the role of the p53 gene in cancer?

The p53 gene is a tumor suppressor that can induce cell cycle arrest or apoptosis in response to DNA damage.

What is the difference between benign and malignant tumors in terms of nuclear size?

Benign tumors have small nuclei, while malignant tumors have large nuclei.

What does a high mitotic index indicate in a tumor?

A high mitotic index indicates a high rate of cell division, which is characteristic of malignant tumors.

How does the clinical stage of cancer differ?

Clinical stage is determined by tumor size (T), lymph node involvement (N), and metastasis (M).

What is the significance of E-cadherin in cancer metastasis?

Loss of E-cadherin is associated with increased motility of cancer cells and their ability to metastasize.

What types of cancer are associated with BRCA1 and BRCA2 mutations?

BRCA1 and BRCA2 mutations are associated with hereditary breast and ovarian cancers.

What is the role of environmental factors in cancer incidence?

Environmental factors, along with heredity and lifestyle, contribute to variations in cancer incidence and death rates.

What is the difference between lymphomas and leukemias?

Lymphomas are solid tumors of lymphocytes, while leukemias involve malignant blood cells proliferating in the bloodstream.

What is the impact of lifestyle on cancer risk?

Lifestyle choices, such as diet and smoking, can significantly influence cancer risk and incidence rates.

What determines the time of onset of detectable cancer?

The duration of exposure to carcinogens.

What is DCIS in cancer terminology?

Ductal Carcinoma in situ, a non-invasive breast cancer.

What does CIN stand for?

Cervical intraepithelial neoplasia.

What is the progression from adenoma to carcinoma?

It involves the transformation of benign growths (adenomas) into malignant tumors (carcinomas).

What is the significance of G6PD in cancer?

Glucose-6-phosphate dehydrogenase is an enzyme that can be involved in cancer metabolism.

What does loss of heterozygosity refer to in cancer genetics?

It refers to the loss of one allele of a gene in a cell that already has a mutation in the other allele.

What role does the APC gene play in colorectal cancer?

The APC tumor suppressor regulates Wnt signaling and mutations in this gene are linked to familial adenomatous polyposis.

What is the relationship between mutations and cancer development?

Cancer development requires both mutations and increased cell proliferation.

What are some mechanisms leading to cancer susceptibility?

Mis-segregation, mitotic recombination, translocation, and point mutations.

What is the role of oncogenes in cancer transformation?

Oncogenes collaborate to induce transformation and promote cancer cell characteristics.

What is the significance of tumor-suppressor genes like p53?

Loss of tumor-suppressor genes can lead to uncontrolled cell growth and cancer.

What is the typical outcome of APC mutations in colon cancer?

100% cancer by age 60 in familial adenomatous polyposis cases.

What does PIN stand for?

Prostatic intraepithelial neoplasia.

What is the role of the TGFβ pathway in cancer?

It inhibits proliferation and can act as a tumor suppressor.

What is the difference between monoclonal and polyclonal tumors?

Monoclonal tumors arise from a single cell, while polyclonal tumors originate from multiple cells.

What is required for the in vitro transformation of cells?

Collaboration of multiple oncogenes.

What is the typical progression of colorectal cancer?

Normal epithelial cells → small benign growth (polyp) → larger benign growth (adenoma) → malignant tumor (carcinoma).

What is the significance of increased proliferation in cancer cells?

It leads to increased invasiveness, survival in the bloodstream, and resistance to immune responses and therapies.

What is the role of the ras oncogene in cancer?

It is involved in cell signaling pathways that promote cell growth and division.

What are Koch's postulates?

1. The suspected pathogen must be detected in diseased tissue and absent from healthy tissue. 2. The pathogen must be isolated and grown in the lab. 3. The lab-grown pathogen must cause the disease in a healthy organism. 4. The isolated pathogen from the new host must be identical to the original.

What significant discovery was made by W. Ellerman and O. Bang in 1908?

They reported that leukemia could be transmitted to healthy chickens by injecting them with blood extracts from diseased chickens.

What is the Rous Sarcoma Virus (RSV) and its significance?

Discovered in 1911, RSV was the first virus identified to cause cancer in animals.

What did R. Shope accomplish in 1933?

He transmitted skin cancer between rabbits using cell-free tumor extracts.

What is the role of the src gene in RSV?

The src gene contains all transforming functions and is associated with triggering sarcomas.

What is the difference between c-src and v-src?

c-src is a cellular gene compatible with normal cell behavior, while v-src is a viral gene that acts as a potent oncogene.

What major award was given for the discovery of the cellular origin of retroviral oncogenes?

The Nobel Prize in Physiology or Medicine in 1989 was awarded to J. Michael Bishop and Harold E. Varmus.

What is insertional mutagenesis?

A process where viral integration into the host genome activates oncogenes, potentially leading to cancer.

Which virus is associated with Burkitt's lymphoma?

Epstein-Barr Virus (EBV) is implicated in Burkitt's lymphoma and other cancers.

What type of cancer is associated with Hepatitis B virus (HBV)?

Liver cancer (hepatocellular carcinoma).

What is the primary cancer associated with Human Papillomavirus (HPV)?

Cervical cancer, as well as anal, oral, and skin cancers.

What are the major biological activities of Human T-cell leukemia virus (HTLV-1)?

HTLV-1 activates proto-oncogenes and inactivates tumor suppressor genes like p53 and pRB.

How is Kaposi's sarcoma-associated herpesvirus (KSHV) transmitted?

Through sexual contact, mother to child, and blood products.

What is the prevalence of Hepatitis C (HCV) in liver cancer cases?

HCV is responsible for 75% of liver cancer cases in certain regions.

What is the role of viral oncoproteins E6 and E7 in HPV?

They inactivate tumor suppressor proteins p53 and pRB, contributing to cancer development.

What is a common characteristic of DNA viruses associated with cancer?

They often encode proteins that can disrupt normal cell cycle regulation and promote tumor formation.

What type of cells does Epstein-Barr Virus (EBV) primarily infect?

B cells and oropharyngeal epithelial cells.

What type of cancer is associated with Hepatitis C virus (HCV)?

Liver cancer.

What are the major biological activities of EBV that contribute to cancer?

EBV can lead to lymphoproliferative disorders and is associated with an increased risk of certain lymphomas.

What is the significance of the src gene in cancer research?

It was the first identified oncogene and is crucial for understanding cancer mechanisms.

What is the relationship between retroviruses and oncogenes?

Retroviruses can acquire cellular oncogenes during their replication, which can lead to cancer.

What is the role of the HBx protein in Hepatitis B virus (HBV)?

HBx affects cellular responses to stress and contributes to liver cancer development.

What is the primary mechanism by which HPV contributes to cancer?

By inactivating tumor suppressor genes and causing mitotic abnormalities.

What is the purpose of gene transfer technology in cancer research?

To detect oncogenes in the DNA of cancer cells.

What is a point mutation in the context of oncogenes?

A change in a single amino acid in a gene, such as the mutation from glycine to valine in RAS oncogenes.

What significant discovery was made using DNA from human bladder cancers?

The first cellular oncogene, RAS, was identified through transfection of normal mouse cells.

In which types of cancer have RAS oncogenes been detected?

Bladder, lung, colon, pancreas, and thyroid cancer.

What is gene amplification and how does it relate to cancer?

The creation of multiple copies of a gene, found in 5-50% of cancer cases, leading to excessive protein production.

Which gene family is associated with gene amplification in various cancers?

The MYC gene family, including MYC, MYCL, and MYCN.

What is the significance of the HER2/ERBB2/neu gene in cancer?

It is amplified in 25% of breast and ovarian cancers, leading to excessive growth factor receptor signaling.

What is the Philadelphia chromosome and its association with cancer?

A chromosomal translocation (BCR-ABL) associated with 90% of chronic myelogenous leukemia (CML).

What type of protein does the BCR-ABL fusion gene code for?

An abnormal version of Abl tyrosine kinase that cannot trigger apoptosis.

What is a reciprocal translocation and its relevance to oncogenes?

A chromosomal rearrangement where a piece of one chromosome moves to another, such as MYC in Burkitt's lymphoma.

What are local DNA rearrangements and their types?

Changes in DNA sequences that disrupt proto-oncogene expression, including deletions, insertions, transpositions, and inversions.

What is the TRK oncogene and its role in cancer?

NTRK1, a growth factor receptor with tyrosine kinase activity, involved in thyroid cancers due to fusion with TPM3.